Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Participants With Dementia of the Alzheimer's Type

Otsuka

Status and phase: Completed; Phase 3

Conditions: Agitation in Participants With Dementia of the Alzheimer's Type

Treatments: Drug: AVP-786-42.63; Drug: AVP-786-18; Drug: Placebo; Drug: AVP-786-28

Study type: Interventional

Funder types: Industry

Identifiers

NCT02442778

15-AVP-786-302

Details and patient eligibility

About

Participants with agitation secondary to dementia of the Alzheimer's type. The diagnosis of probable Alzheimer's disease (AD) will be based on the "2011 Diagnostic Guidelines for Alzheimer's Disease" issued by the National Institute on Aging (NIA)-Alzheimer's Association (AA) workgroups.

Full description

Eligible participants for this study must have a diagnosis of probable AD and must have clinically meaningful agitation secondary to AD.

This is a multicenter, randomized, placebo-controlled study, consisting of 12 weeks of treatment.

Approximately 470 participants will be enrolled at approximately 75 centers in North America.

Study medication will be administered orally twice-daily from Day 1 through Week 12 (Day 85). Screening will occur within approximately 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants will be randomized into the study.

Enrollment: 522 patients

Sex: All

Ages: 50 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of probable Alzheimer's Disease (AD) according to the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) working groups criteria
• The participant has clinically significant, moderate/severe agitation at the time of screening and for at least 2 weeks prior to randomization
• The diagnosis of agitation must meet the International Psychogeriatric Association (IPA) provisional definition of agitation
• Either out participants or residents of an assisted-living facility or a skilled nursing home
• Clinical Global Impression of Severity of Illness (CGIS) score assessing Agitation is >=4 (moderately ill) at screening and baseline
• Mini-Mental State Examination (MMSE) score is between 6 and 26 (inclusive) at screening and baseline
• Caregiver who is able and willing to comply with all required study procedures. In order to qualify as a reliable informant (i.e., caregiver) capable of assessing changes in participant's condition during the study, the individual must spend a minimum of 2 hours per day for 4 days per week with the participant.

Exclusion criteria

• Participant has dementia predominantly of non-Alzheimer's type (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia)
• Participants with co-existent clinically significant or unstable systemic diseases that could confound the interpretation of the safety results of the study (e.g., malignancy, poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, or unstable valvular heart disease)
• Participant with myasthenia gravis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

522 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants were administered AVP-786 matching placebo capsules, orally, twice daily (BID) for up to 12 weeks.

Treatment:

Drug: Placebo

AVP-786-28

Experimental group

Description:

Participants were administered AVP-786-18 capsule, orally, once daily (QD) along with AVP-786 matching placebo capsule, orally, QD during Week 1 followed by AVP-786-18 capsules, orally, BID during Weeks 2, 3 and AVP-786-28 capsules, orally, BID during Weeks 4 to 12.

Treatment:

Drug: AVP-786-28

Drug: AVP-786-18

AVP-786-42.63

Experimental group

Description:

Participants were administered AVP-786-28 capsules, orally, QD along with AVP-786 matching placebo capsule, orally, QD during Week 1 followed by AVP-786-28 capsules, orally, BID during Weeks 2, 3, and AVP-786-42.63 capsules, orally, BID during Weeks 4 to 12.

Treatment:

Drug: AVP-786-28

Drug: AVP-786-42.63